1376:
312:
1512:. Pembrolizumab has been made accessible to advanced melanoma patients in the UK via UK Early Access to Medicines Scheme (EAMS) in March 2015. It is being used in clinical trials in the US for lung cancer, lymphoma, and mesothelioma. It has had measured success, with little side effects. It is up to the manufacturer of the drug to submit application to the FDA for approval for use in these diseases. On October 2, 2015, Pembrolizumab was approved by FDA for advanced (metastatic) non-small cell lung cancer (NSCLC) patients whose disease has progressed after other treatments.
289:
211:
186:
563:
1434:
CD8+ T cells that are actively infiltrating the tumor tissue. The authors hypothesized that the higher levels of CD8+ T cell infiltration was due to anti-CTLA-4 inhibited the conversion of CD4 T cells to T regulator cells and further reduced T regulatory suppression with anti-PD-1. This combination promoted a more robust inflammatory response to the tumor that reduced the size of the cancer. Most recently, the FDA has approved a combination therapy with both anti-CTLA4 (
318:
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31:
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tissue. Repeated administrations with anti-PD-1 were found to be necessary to maintain the therapeutic effects of the treatment. Amyloid fibrils are immunosuppressive and this finding has been separately confirmed by examining the effects of the fibrils in neuroinflammatory diseases. PD-1 counteracts the effects of the fibrils by boosting immune activity and triggering an immune pathway that allows for brain repair.
1449:
expression on the surface on cancer cells plays a significant role. PD-L1 positive tumors were twice as likely to respond to combination treatment. However patients with PD-L1 negative tumors also have limited response to anti-PD1, demonstrating that PD-L1 expression is not an absolute determinant of
1433:
In clinical trials, combination therapy has been shown to be effective in reducing tumor size in patients that are unresponsive to single co-inhibitory blockade, despite increasing levels of toxicity due to anti-CTLA4 treatment. A combination of PD1 and CTLA4 induced up to a ten-fold higher number of
1306:
stimulated T cells with PD-L1-Ig results in reduced T cell proliferation and IFN-γ secretion. IFN-γ is a key pro-inflammatory cytokine that promotes T cell inflammatory activity. Reduced T cell proliferation was also correlated with attenuated IL-2 secretion and together, these data suggest that PD-1
3265:
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia
2215:
Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, Iwai Y, Long AJ, Brown JA, Nunes R, Greenfield EA, Bourque K, Boussiotis VA, Carter LL, Carreno BM, Malenkovich N, Nishimura H, Okazaki T, Honjo T, Sharpe AH, Freeman GJ (March 2001). "PD-L2 is a second ligand for PD-1 and inhibits T
1579:
Blocking of PD-1 leads to a reduction in cerebral amyloid-β plaques and improves cognitive performance in mice. Immune blockade of PD-1 evoked an IFN-γ dependent immune response that recruited monocyte-derived macrophages to the brain that were then capable of clearing the amyloid-β plaques from the
1327:
Expression of PD-L1 on tumor cells inhibits anti-tumor activity through engagement of PD-1 on effector T cells. Expression of PD-L1 on tumors is correlated with reduced survival in esophageal, pancreatic and other types of cancers, highlighting this pathway as a target for immunotherapy. Triggering
3885:
Prokunina L, Castillejo-López C, Oberg F, Gunnarsson I, Berg L, Magnusson V, Brookes AJ, Tentler D, Kristjansdóttir H, Gröndal G, Bolstad AI, Svenungsson E, Lundberg I, Sturfelt G, Jönssen A, Truedsson L, Lima G, Alcocer-Varela J, Jonsson R, Gyllensten UB, Harley JB, Alarcón-Segovia D, Steinsson K,
1570:
eradication. T lymphocytes exhibit elevated expression of PD-1 in cases of chronic HIV infection. Heightened presence of the PD-1 receptors corresponds to exhaustion of the HIV specific CD8+ cytotoxic and CD4+ helper T cell populations that are vital in combating the virus. Immune blockade of PD-1
1453:
Higher mutational burden in the tumor is correlated with a greater effect of the anti-PD-1 treatment. In clinical trials, patients who benefited from anti-PD1 treatment had cancers, such as melanoma, bladder cancer, and gastric cancer, that had a median higher average number of mutations than the
1425:
A combination of PD1 and CTLA4 antibodies has been shown to be more effective than either antibody alone in the treatment of a variety of cancers. The effects of the two antibodies do not appear to be redundant. Anti-CTLA4 treatment leads to an enhanced antigen specific T cell dependent immune
57:
4119:
Prokunina L, Padyukov L, Bennet A, de Faire U, Wiman B, Prince J, Alfredsson L, Klareskog L, Alarcón-Riquelme M (June 2004). "Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope".
1323:
viral vector model of chronic infection, Rafi Ahmed's group showed that the PD-1-PD-L1 interaction inhibits activation, expansion and acquisition of effector functions of virus specific CD8 T cells, which can be reversed by blocking the PD-1-PD-L1 interaction.
3587:
Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, Matcovitch-Natan O, Kertser A, David E, Amit I, Schwartz M (February 2016). "PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of
Alzheimer's disease".
4340:
Kobayashi M, Kawano S, Hatachi S, Kurimoto C, Okazaki T, Iwai Y, Honjo T, Tanaka Y, Minato N, Komori T, Maeda S, Kumagai S (November 2005). "Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjögren's syndrome".
2895:
Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (November 2014).
3478:
Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS, Hammond KB, Clayton KL, Ishii N, Abdel-Mohsen M, Liegler T, Mitchell BI, Hecht FM, Ostrowski M, Shikuma CM, Hansen SG, Maurer M, Korman AJ, Deeks SG, Sacha JB, Ndhlovu LC (January 2016).
2953:
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA (December 2014).
4149:
Sanghera DK, Manzi S, Bontempo F, Nestlerode C, Kamboh MI (October 2004). "Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies".
4059:
Prokunina L, Gunnarsson I, Sturfelt G, Truedsson L, Seligman VA, Olson JL, Seldin MF, Criswell LA, Alarcón-Riquelme ME (January 2004). "The systemic lupus erythematosus-associated PDCD1 polymorphism PD1.3A in lupus nephritis".
1318:
T cells suggest that CD8 T cells are more susceptible to inhibition by PD-L1, although this could be dependent on the strength of TCR signaling. Consistent with a role in negatively regulating CD8 T cell responses, using an
1165:
in 1992 discovered and named PD-1. In 1999, the same group demonstrated that mice where PD-1 was knocked down were prone to autoimmune disease and hence concluded that PD-1 was a negative regulator of immune responses.
4187:
Nielsen C, Laustrup H, Voss A, Junker P, Husby S, Lillevang ST (2005). "A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients".
2624:
Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, Hill BJ, Noto A, Ancuta P, Peretz Y, Fonseca SG, Van
Grevenynghe J, Boulassel MR, Bruneau J, Shoukry NH, Routy JP, Douek DC, Haddad EK, Sekaly RP (April 2010).
2162:
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (October 2000).
4089:
Lin SC, Yen JH, Tsai JJ, Tsai WC, Ou TT, Liu HW, Chen CJ (March 2004). "Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus".
325:
224:
1494:), produced complete or partial responses in non-small-cell lung cancer, melanoma, and renal-cell cancer, in a clinical trial with a total of 296 patients. Colon and pancreatic cancer did not have a response.
2447:
Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, Sasayama S, Mizoguchi A, Hiai H, Minato N, Honjo T (January 2001). "Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice".
3925:"Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses"
4001:
Youngnak P, Kozono Y, Kozono H, Iwai H, Otsuki N, Jin H, Omura K, Yagita H, Pardoll DM, Chen L, Azuma M (August 2003). "Differential binding properties of B7-H1 and B7-DC to programmed death-1".
4030:
Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST (December 2003). "Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes".
2532:
Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R (February 2006). "Restoring function in exhausted CD8 T cells during chronic viral infection".
2120:
Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T (May 1996). "Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes".
1454:
patients who did not respond to the therapy. However, the correlation between higher tumor burden and the clinical effectiveness of PD-1 immune blockade is still uncertain.
1881:
1274:
can be detected in the heart, lung, thymus, spleen, and kidney. PD-L1 is expressed on almost all murine tumor cell lines, including PA1 myeloma, P815 mastocytoma, and
4239:
Johansson M, Arlestig L, Möller B, Rantapää-Dahlqvist S (June 2005). "Association of a PDCD1 polymorphism with renal manifestations in systemic lupus erythematosus".
5296:
2583:
Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, Mizuno T, Yoriki R, Kashizuka H, Yane K, Tsushima F, Otsuki N, Yagita H, Azuma M, Nakajima Y (April 2005).
2825:
Gandini S, Massi D, Mandalà M (April 2016). "PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis".
4435:
3792:
Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR (April 1997). "Activation-induced expression of human programmed death-1 gene in T-lymphocytes".
1328:
PD-1, expressed on monocytes and up-regulated upon monocytes activation, by its ligand PD-L1 induces IL-10 production which inhibits CD4 T-cell function.
3415:
786:
3886:
Alarcón-Riquelme ME (December 2002). "A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans".
767:
147:
1403:. Many tumor cells express PD-L1, an immunosuppressive PD-1 ligand; inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses
4231:
3923:
Bennett F, Luxenberg D, Ling V, Wang IM, Marquette K, Lowe D, Khan N, Veldman G, Jacobs KA, Valge-Archer VE, Collins M, Carreno BM (January 2003).
1267:
6472:
1674:
Shinohara T, Taniwaki M, Ishida Y, Kawaichi M, Honjo T (October 1994). "Structure and chromosomal localization of the human PD-1 gene (PDCD1)".
5286:
2860:
Weber J (October 2010). "Immune checkpoint proteins: a new therapeutic paradigm for cancer--preclinical background: CTLA-4 and PD-1 blockade".
1207:
4413:
1656:
3481:"TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection"
1638:
3680:
Kurnellas MP, Ghosn EE, Schartner JM, Baker J, Rothbard JJ, Negrin RS, Herzenberg LA, Fathman CG, Steinman L, Rothbard JB (December 2015).
1530:
1391:
PD-L1, the ligand for PD1, is highly expressed in several cancers and hence the role of PD1 in cancer immune evasion is well established.
3057:"PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors"
5266:
4403:
3856:
Iwai Y, Okazaki T, Nishimura H, Kawasaki A, Yagita H, Honjo T (October 2002). "Microanatomical localization of PD-1 in human tonsils".
2259:
Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, Shin T, Tsuchiya H, Pardoll DM, Okumura K, Azuma M, Yagita H (November 2002).
990:
6128:
4452:
4428:
2165:"Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation"
997:
1126:, a new class of drugs that block PD-1, activate the immune system to attack tumors and are used to treat certain types of cancer.
4297:
Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, Linsley PS, Thompson CB, Riley JL (November 2005).
5859:
2016:"Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion"
1714:
4268:
Nielsen C, Ohm-Laursen L, Barington T, Husby S, Lillevang ST (June 2005). "Alternative splice variants of the human PD-1 gene".
5847:
5625:
1222:
phosphatases to the cytoplasmic tail of PD-1 upon ligand binding. In addition, PD-1 ligation up-regulates E3-ubiquitin ligases
2509:
2492:
5911:
5906:
5852:
5632:
2408:"Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor"
2585:"Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer"
1621:
1089:'s response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing
6562:
6557:
5365:
5291:
4421:
1518:
is a humanized IgG4 monoclonal antibody against PD-1 which was approved in China in 2018 and in the United States in 2023.
54:
3823:"The human PD-1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors"
1600:
6465:
6394:
6389:
6384:
6379:
5306:
3311:
1498:(Opdivo, Bristol-Myers Squibb) was approved in Japan in July 2014 and by the US FDA in December 2014 to treat metastatic
1508:(Keytruda, MK-3475, Merck), which also targets PD-1 receptors, was approved by the FDA in Sept 2014 to treat metastatic
2627:"Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection"
1195:
6359:
2305:"Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade"
1331:
In mice, expression of this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of
3960:"Molecular modeling and functional mapping of B7-H1 and B7-DC uncouple costimulatory function from PD-1 interaction"
311:
5595:
1745:
Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting".
1375:
5657:
5343:
2491:
Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR, Collins M, Honjo T, Freeman GJ, Carreno BM (March 2002).
1625:
1604:
1210:
and an immunoreceptor tyrosine-based switch motif, which suggests that PD-1 negatively regulates T-cell receptor
288:
6458:
5802:
5338:
1913:"Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death"
1226:
and c-CBL that trigger T cell receptor down-modulation. PD-1 is expressed on the surface of activated T cells,
835:
4443:
3741:"Mechanisms of action of therapeutic amyloidogenic hexapeptides in amelioration of inflammatory brain disease"
1445:
The molecular factors and receptors necessary making a tumor receptive to anti-PD1 treatment remains unknown.
6299:
5771:
5766:
5711:
5445:
4894:
2367:"PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells"
1270:
treatment, and on T cells and B cells upon TCR and B cell receptor signaling, whereas in resting mice, PD-L1
1829:
Fife BT, Pauken KE (January 2011). "The role of the PD-1 pathway in autoimmunity and peripheral tolerance".
816:
812:
5993:
5716:
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210:
185:
127:
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resulted in restoration of T cell inflammatory phenotype necessary to combat the progression of disease.
324:
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6023:
4448:
1408:
1290:
Several lines of evidence suggest that PD-1 and its ligands negatively regulate immune responses. PD-1
1130:
1059:
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Finger LR, Pu J, Wasserman R, Vibhakar R, Louie E, Hardy RR, Burrows PD, Billips LG (September 1997).
317:
216:
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1478:
6450:
2073:"PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells"
114:
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4373:
2122:
1458:
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135:
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973:
952:
926:
905:
6567:
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5375:
5370:
5360:
4667:
4595:
1340:
1234:, suggesting that compared to CTLA-4, PD-1 more broadly negatively regulates immune responses.
1562:
Drugs targeting PD-1 in combination with other negative immune checkpoint receptors, such as (
4724:
4642:
4225:
2493:"PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2"
1419:
1392:
1243:
1134:
1074:
2723:
Müller T, Braun M, Dietrich D, Aktekin S, Höft S, Kristiansen G, et al. (August 2017).
2071:
Karwacz K, Bricogne C, MacDonald D, Arce F, Bennett CL, Collins M, Escors D (October 2011).
1282:. PD-L2 expression is more restricted and is expressed mainly by DCs and a few tumor lines.
6537:
6485:
5961:
5674:
3693:
3123:
3068:
3005:"CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition"
2909:
2898:"Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients"
2541:
2457:
2316:
1838:
1522:
1491:
1483:
A number of cancer immunotherapy agents that target the PD-1 receptor have been developed.
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8:
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Kurnellas MP, Schartner JM, Fathman CG, Jagger A, Steinman L, Rothbard JB (August 2014).
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3127:
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Blank C, Brown I, Peterson AC, Spiotto M, Iwai Y, Honjo T, Gajewski TF (February 2004).
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2015:
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3535:"Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options"
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1996:
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1469:"for their discovery of cancer therapy by inhibition of negative immune regulation".
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1101:
107:
47:
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3915:
3682:"Amyloid fibrils activate B-1a lymphocytes to ameliorate inflammatory brain disease"
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3218:"Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy"
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on the C57BL/6 and BALB/c backgrounds, respectively. In vitro, treatment of anti-
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National Center for
Biotechnology Information, U.S. National Library of Medicine
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National Center for
Biotechnology Information, U.S. National Library of Medicine
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Proceedings of the
National Academy of Sciences of the United States of America
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Proceedings of the
National Academy of Sciences of the United States of America
2764:- "Figure 1 - available via license: Creative Commons Attribution 3.0 Unported"
2309:
Proceedings of the
National Academy of Sciences of the United States of America
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1123:
480:
4163:
3551:
3446:
3114:
Sliwkowski MX, Mellman I (September 2013). "Antibody therapeutics in cancer".
2776:"PD-L1 expression in human cancers and its association with clinical outcomes"
2740:
2725:"PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma"
2031:
6551:
5983:
5440:
4531:
4407:
2691:
2135:
1981:
1505:
1396:
1311:
1291:
1199:
1086:
591:
4299:"CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms"
3706:
3633:"Amyloid fibrils composed of hexameric peptides attenuate neuroinflammation"
3135:
3081:
1601:
ENSG00000276977 GRCh38: Ensembl release 89: ENSG00000188389, ENSG00000276977
1418:
therapeutics have emerged as important tumor treatments within the field of
1310:
Experiments using PD-L1 transfected DCs and PD-1 expressing transgenic (Tg)
609:
562:
540:
418:
6533:
What I Talk about When I Talk about the
Discovery of PD-1 (Yasumasa Ishida)
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3725:
3666:
3609:
3570:
3516:
3464:
3401:
3301:
3251:
3195:
3143:
3100:
3038:
2989:
2939:
2881:
2846:
2811:
2758:
2709:
2660:
2610:
2561:
2518:
2477:
2433:
2392:
2348:
2329:
2303:
Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N (September 2002).
2286:
2237:
2198:
2180:
2106:
2088:
2049:
2000:
1858:
1815:
1766:
1687:
1534:
1466:
1275:
1255:
1158:
1104:
and guards against autoimmunity through two mechanisms. First, it promotes
397:
176:
3848:
3813:
3283:
2971:
2143:
1946:
1695:
1037:
1032:
6532:
6349:
5998:
5776:
5751:
5450:
5072:
4998:
4472:
4238:
3975:
3756:
3586:
3268:"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer"
1882:"New Bristol-Myers Drug Helped Skin-Cancer Patients in Trial Live Longer"
1526:
1515:
880:
861:
3884:
3631:
Kurnellas MP, Adams CM, Sobel RA, Steinman L, Rothbard JB (April 2013).
3233:
2921:
2792:
2553:
1387:, demonstrating negative (A), low (B), and high (C) PD-L1 protein levels
1347:. These studies suggest that this gene product may also be important in
6279:
6003:
5684:
5425:
5301:
4934:
4929:
4924:
4779:
4563:
1542:
1435:
1231:
1223:
1179:
1113:
1097:, but it can also prevent the immune system from killing cancer cells.
296:
193:
143:
118:, CD279, PD-1, PD1, SLEB2, hPD-1, hPD-l, hSLE1, Programmed cell death 1
4252:
4133:
4103:
4073:
1202:
region and an intracellular tail. The intracellular tail contains two
84:
80:
76:
6480:
6118:
6113:
6108:
6098:
6093:
6088:
6083:
2510:
10.1002/1521-4141(200203)32:3<634::AID-IMMU634>3.0.CO;2-9
1495:
1487:
1439:
1339:. Mice deficient for this gene bred on a BALB/c background developed
1336:
1332:
1154:
1105:
731:
363:
350:
262:
249:
151:
4058:
3601:
2956:"Genetic basis for clinical response to CTLA-4 blockade in melanoma"
2642:
2261:"Expression of programmed death 1 ligands by murine T cells and APC"
6424:
6324:
6138:
6123:
5326:
5321:
5229:
4919:
3899:
1965:"The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation"
1538:
1509:
1499:
1021:
30:
3958:
Wang S, Bajorath J, Flies DB, Dong H, Honjo T, Chen L (May 2003).
2229:
1358:
Overexpression of PD1 on CD8+ T cells is one of the indicators of
6374:
6369:
6364:
6264:
6078:
6068:
5895:
5874:
5869:
5837:
5642:
5562:
5557:
5552:
5547:
5542:
5460:
5153:
4993:
4988:
4983:
4978:
4973:
4444:
4394:
4384:
3791:
1109:
1063:
847:
798:
716:
712:
4267:
131:
6509:
6314:
6274:
6259:
6243:
6238:
6218:
6213:
6148:
5956:
5926:
5890:
5881:
5694:
5662:
5526:
5521:
5491:
5470:
5430:
5390:
5256:
5234:
5193:
5117:
5112:
5107:
5102:
5097:
5092:
4961:
4956:
4951:
4899:
4884:
4754:
4744:
4707:
4702:
4620:
4615:
4296:
4148:
4118:
3738:
3333:"FDA approves Keytruda for advanced non-small cell lung cancer"
1673:
1546:
1415:
1400:
1348:
1227:
1219:
1191:
1187:
1090:
1082:
1078:
1005:
753:
571:
4339:
2446:
2406:
Nishimura H, Nose M, Hiai H, Minato N, Honjo T (August 1999).
1194:
regulators. The protein's structure includes an extracellular
6514:
6439:
6414:
6334:
6329:
6319:
6309:
6294:
6289:
6284:
6269:
6223:
6208:
6173:
6158:
6153:
6143:
6063:
6058:
6053:
6032:
6028:
6018:
5931:
5832:
5827:
5786:
5736:
5731:
5726:
5721:
5706:
5699:
5679:
5667:
5610:
5605:
5600:
5590:
5585:
5578:
5516:
5506:
5501:
5496:
5486:
5465:
5455:
5420:
5415:
5410:
5405:
5400:
5355:
5350:
5316:
5281:
5276:
5271:
5261:
5249:
5244:
5224:
5219:
5214:
5209:
5163:
5055:
5050:
4869:
4853:
4846:
4841:
4836:
4831:
4826:
4821:
4796:
4774:
4769:
4662:
4588:
4583:
4573:
2214:
1563:
1446:
1407:
and mediate preclinical antitumor activity. This is known as
1251:
1247:
1215:
1142:
1138:
4379:
Overview of all the structural information available in the
3855:
3679:
3431:"Role of PD-1 in HIV pathogenesis and as target for therapy"
3416:"FDA approves toripalimab-tpzi for nasopharyngeal carcinoma"
3264:
2119:
2070:
1133:
and is expressed on T cells and pro-B cells. PD-1 binds two
6519:
6504:
6499:
6434:
6429:
6419:
6409:
6404:
6399:
6354:
6344:
6304:
6233:
6203:
6198:
6193:
6188:
6183:
6178:
6133:
6103:
6008:
5976:
5971:
5951:
5941:
5936:
5921:
5916:
5817:
5812:
5781:
5761:
5756:
5746:
5741:
5620:
5573:
5533:
5188:
5183:
5178:
5173:
5158:
5149:
5144:
5139:
5124:
5082:
5077:
5067:
5062:
5045:
5040:
5035:
5030:
5025:
5020:
5015:
5010:
5005:
4941:
4914:
4909:
4904:
4879:
4874:
4811:
4806:
4801:
4791:
4786:
4739:
4734:
4729:
4719:
4714:
4697:
4692:
4687:
4677:
4672:
4657:
4652:
4647:
4637:
4632:
4627:
4610:
4605:
4600:
4551:
4519:
4514:
4509:
4492:
4487:
4482:
4477:
3630:
3054:
1962:
1521:
Drugs in early stage development targeting PD-1 receptors (
1320:
1271:
1183:
1070:
4029:
3533:
Velu V, Shetty RD, Larsson M, Shankar EM (February 2015).
3215:
3055:
Curran MA, Montalvo W, Yagita H, Allison JP (March 2010).
2722:
5946:
4558:
4546:
4541:
4536:
4526:
4499:
4467:
4186:
3820:
3351:"Toripalimab - Shanghai Junshi Biosciences - AdisInsight"
3216:
Topalian SL, Taube JM, Anders RA, Pardoll DM (May 2016).
2952:
2364:
1911:
Ishida Y, Agata Y, Shibahara K, Honjo T (November 1992).
1910:
1567:
4000:
3922:
3532:
2258:
1414:
Combination therapy using both anti-PD1 along with anti-
1258:
family. PD-L1 protein is upregulated on macrophages and
387:
2894:
2623:
2582:
2531:
2405:
2302:
3170:"Oncology meets immunology: the cancer-immunity cycle"
2676:"Overcoming T cell exhaustion in infection and cancer"
2490:
2161:
3957:
3477:
3337:
552:
3418:. US Food and Drug Administration. October 27, 2023.
1129:
PD-1 is a cell surface receptor that belongs to the
4003:
2824:
1779:
3310:
1617:
1615:
1613:
1596:
1594:
1592:
1566:), may augment immune responses and/or facilitate
3582:
3580:
3113:
334:
233:
6549:
3428:
3266:GD, Gupta A, Wigginton JM, Sznol M (June 2012).
3211:
3209:
3207:
3205:
2210:
2208:
1782:"The PD-1 pathway in tolerance and autoimmunity"
3471:
3163:
3161:
3002:
2157:
2155:
2153:
1963:Bardhan K, Anagnostou T, Boussiotis VA (2016).
1958:
1956:
1610:
1589:
1426:reaction while anti-PD-1 appears to reactivate
677:positive regulation of T cell apoptotic process
4088:
3577:
3308:
2773:
2013:
1906:
1904:
1902:
1780:Francisco LM, Sage PT, Sharpe AH (July 2010).
1622:GRCm38: Ensembl release 89: ENSMUSG00000026285
1208:immunoreceptor tyrosine-based inhibitory motif
6466:
4429:
4230:: CS1 maint: DOI inactive as of April 2024 (
3258:
3202:
3050:
3048:
2360:
2358:
2205:
1744:
1351:function and contribute to the prevention of
3422:
3158:
2853:
2818:
2774:Wang X, Teng F, Kong L, Yu J (August 2016).
2767:
2673:
2617:
2576:
2525:
2484:
2440:
2399:
2298:
2296:
2252:
2150:
2064:
2007:
1953:
1715:"Entrez Gene: PDCD1 programmed cell death 1"
1214:signals. This is consistent with binding of
3167:
2716:
2113:
1899:
1822:
1773:
6473:
6459:
4436:
4422:
4404:United States National Library of Medicine
3528:
3526:
3373:
3045:
2667:
2355:
1831:Annals of the New York Academy of Sciences
1828:
1667:
1120:(anti-inflammatory, suppressive T cells).
687:negative regulation of tolerance induction
4453:list of human clusters of differentiation
4393:(Programmed cell death protein 1) at the
4372:at the U.S. National Library of Medicine
4322:
3983:
3940:
3838:
3764:
3715:
3705:
3656:
3560:
3550:
3506:
3496:
3454:
3391:
3291:
3241:
3185:
3090:
3080:
3028:
2979:
2929:
2801:
2791:
2748:
2699:
2650:
2600:
2508:
2423:
2382:
2338:
2328:
2293:
2276:
2188:
2096:
2039:
1990:
1980:
1936:
1805:
1472:
1399:are being developed for the treatment of
4402:This article incorporates text from the
3312:"Drug Helps Defense System Fight Cancer"
3003:Buchbinder EI, Desai A (February 2016).
1709:
1707:
1705:
1374:
1365:
672:negative regulation of apoptotic process
657:positive regulation of apoptotic process
3523:
2827:Critical Reviews in Oncology/Hematology
1362:(e.g. in chronic infection or cancer).
1307:negatively regulates T cell responses.
6550:
3429:Porichis F, Kaufmann DE (March 2012).
1879:
1574:
1294:have been shown to develop lupus-like
6538:PD-1_Project PD-1 project - Honjo Lab
6454:
4417:
3009:American Journal of Clinical Oncology
2859:
1702:
1549:) target the similar PD-L1 receptor.
1093:inflammatory activity. This prevents
339:
300:
295:
238:
197:
192:
3964:The Journal of Experimental Medicine
3745:The Journal of Experimental Medicine
3376:"Toripalimab: First Global Approval"
3367:
2169:The Journal of Experimental Medicine
1740:
1738:
1736:
1734:
1732:
1730:
1728:
1726:
1724:
6543:PD-1プロジェクト(in Japanese) - Honjo Lab
3272:The New England Journal of Medicine
2960:The New England Journal of Medicine
1873:
1182:. PD-1 is a member of the extended
13:
3784:
1929:10.1002/j.1460-2075.1992.tb05481.x
1486:One such anti-PD-1 antibody drug,
1153:In a screen for genes involved in
1116:. Second, it reduces apoptosis in
1085:that has a role in regulating the
662:multicellular organism development
14:
6579:
4363:
2014:Blank C, Mackensen A (May 2007).
1721:
1552:
16:Mammalian protein found in humans
4315:10.1128/MCB.25.21.9543-9553.2005
4044:10.1046/j.1399-0039.2003.00136.x
3168:Chen DS, Mellman I (July 2013).
2874:10.1053/j.seminoncol.2010.09.005
2839:10.1016/j.critrevonc.2016.02.001
2020:Cancer Immunology, Immunotherapy
1851:10.1111/j.1749-6632.2010.05919.x
1798:10.1111/j.1600-065X.2010.00923.x
1379:PD-L1 expression by chromogenic
641:external side of plasma membrane
561:
323:
316:
310:
287:
222:
215:
209:
184:
29:
3732:
3673:
3624:
3408:
3343:
3325:
3309:Andrew Pollack (June 1, 2012).
3107:
2996:
2946:
2888:
1050:Programmed cell death protein 1
4303:Molecular and Cellular Biology
3637:Science Translational Medicine
2497:European Journal of Immunology
1649:
1631:
1543:Merck KGaA, Darmstadt, Germany
1533:(Bristol Myers Squibb). Both
1450:the effectiveness of therapy.
1430:ability to lyse cancer cells.
1395:targeting PD-1 that boost the
626:integral component of membrane
572:More reference expression data
541:More reference expression data
1:
4282:10.1016/j.cellimm.2005.07.007
4015:10.1016/S0006-291X(03)01257-9
3870:10.1016/S0165-2478(02)00088-3
3840:10.1016/S0378-1119(97)00260-6
2674:Pauken KE, Wherry EJ (2015).
2602:10.1158/1078-0432.CCR-04-1469
2425:10.1016/S1074-7613(00)80089-8
2384:10.1158/0008-5472.CAN-03-3259
1759:10.1016/s1470-2045(17)30607-1
1583:
308:
207:
3649:10.1126/scitranslmed.3005681
3498:10.1371/journal.ppat.1005349
3187:10.1016/j.immuni.2013.07.012
3021:10.1097/COC.0000000000000239
2470:10.1126/science.291.5502.319
2278:10.4049/jimmunol.169.10.5538
1169:
1148:
7:
6563:Clusters of differentiation
6558:Genes on human chromosome 2
4449:clusters of differentiation
4343:The Journal of Rheumatology
1285:
1254:, which are members of the
1108:(programmed cell death) of
10:
6584:
6482:Immunoglobulin superfamily
4202:10.1191/0961203303lu1052oa
3942:10.4049/jimmunol.170.2.711
3794:Experimental Cell Research
3393:10.1007/s40265-019-01076-2
1476:
1409:immune checkpoint blockade
1383:in cases of head and neck
1237:
1131:immunoglobulin superfamily
1060:cluster of differentiation
610:signal transducer activity
457:mucosa of transverse colon
6492:
6252:
6046:
5795:
5479:
5202:
4862:
4460:
4164:10.1007/s00439-004-1172-0
3552:10.1186/s12977-015-0144-x
3447:10.1007/s11904-011-0106-4
2741:10.18632/oncotarget.17547
2032:10.1007/s00262-006-0272-1
1657:"Mouse PubMed Reference:"
1639:"Human PubMed Reference:"
1479:PD-1 and PD-L1 inhibitors
1370:
1066:encoded in humans by the
1036:
1031:
1027:
1020:
1004:
991:Chr 2: 241.85 – 241.86 Mb
985:
970:
966:
949:
945:
938:
923:
919:
902:
898:
891:
878:
874:
859:
855:
846:
833:
829:
810:
806:
797:
784:
780:
765:
761:
752:
737:
730:
726:
710:
590:
586:
569:
560:
551:
538:
487:
478:
425:
416:
386:
378:
374:
357:
344:
307:
286:
277:
273:
256:
243:
206:
183:
174:
170:
125:
122:
112:
105:
100:
73:
68:
51:
46:
41:
37:
28:
23:
4374:Medical Subject Headings
4241:Arthritis and Rheumatism
4122:Arthritis and Rheumatism
4092:Arthritis and Rheumatism
4062:Arthritis and Rheumatism
3435:Current HIV/AIDS Reports
3355:adisinsight.springer.com
2692:10.1016/j.it.2015.02.008
2589:Clinical Cancer Research
2123:International Immunology
1982:10.3389/fimmu.2016.00550
1880:Loftus P (16 Nov 2014).
1529:(CT-011, Cure Tech) and
1459:Nobel Prize for Medicine
1345:congestive heart failure
4204:(inactive 2024-04-12).
3707:10.1073/pnas.1521206112
3136:10.1126/science.1241145
3082:10.1073/pnas.0915174107
2780:OncoTargets and Therapy
2077:EMBO Molecular Medicine
1969:Frontiers in Immunology
1537:(MPDL3280A, Roche) and
1385:squamous cell carcinoma
998:Chr 1: 93.97 – 93.98 Mb
682:humoral immune response
461:upper lobe of left lung
3806:10.1006/excr.1997.3493
3222:Nature Reviews. Cancer
2330:10.1073/pnas.192461099
2181:10.1084/jem.192.7.1027
2136:10.1093/intimm/8.5.765
2089:10.1002/emmm.201100165
1688:10.1006/geno.1994.1562
1557:
1473:Anti-PD-1 therapeutics
1388:
1341:dilated cardiomyopathy
503:mesenteric lymph nodes
6486:CD28 family receptors
3929:Journal of Immunology
3284:10.1056/NEJMoa1200690
2972:10.1056/nejmoa1406498
2265:Journal of Immunology
1786:Immunological Reviews
1523:checkpoint inhibitors
1420:checkpoint inhibition
1393:Monoclonal antibodies
1378:
1366:Clinical significance
1198:domain followed by a
1112:-specific T-cells in
1075:cell surface receptor
692:immune system process
4370:PDCD1+protein,+human
3976:10.1084/jem.20021752
3757:10.1084/jem.20140107
2862:Seminars in Oncology
2680:Trends in Immunology
1747:The Lancet. Oncology
1492:Bristol Myers Squibb
1381:immunohistochemistry
1278:upon treatment with
1262:(DC) in response to
1206:sites located in an
667:T cell costimulation
302:Chromosome 1 (mouse)
200:Chromosome 2 (human)
69:List of PDB id codes
42:Available structures
4270:Cellular Immunology
3698:2015PNAS..11215016K
3374:Keam, S.J. (2019).
3234:10.1038/nrc.2016.36
3128:2013Sci...341.1192S
3073:2010PNAS..107.4275C
2922:10.1038/nature14011
2914:2014Natur.515..563H
2793:10.2147/OTT.S105862
2735:(32): 52889–52900.
2554:10.1038/nature04444
2546:2006Natur.439..682B
2462:2001Sci...291..319N
2321:2002PNAS...9912293I
1886:Wall Street Journal
1843:2011NYASA1217...45F
1575:Alzheimer's disease
1442:) in October 2015.
1353:autoimmune diseases
1157:, Yasumasa Ishida,
1095:autoimmune diseases
702:signal transduction
4406:, which is in the
3858:Immunology Letters
3317:The New York Times
2216:cell activation".
1389:
1296:glomerulonephritis
1161:and colleagues at
1118:regulatory T cells
836:ENSMUSG00000026285
650:Biological process
619:Cellular component
598:Molecular function
6528:
6527:
6448:
6447:
4253:10.1002/art.21058
4134:10.1002/art.20280
4104:10.1002/art.20040
4074:10.1002/art.11442
3339:. 2 October 2015.
2218:Nature Immunology
1753:(12): e731–e741.
1360:T-cell exhaustion
1174:PD-1 is a type I
1102:immune checkpoint
1047:
1046:
1043:
1042:
1016:
1015:
981:
980:
960:
959:
934:
933:
913:
912:
887:
886:
868:
867:
842:
841:
823:
822:
793:
792:
774:
773:
722:
721:
697:apoptotic process
582:
581:
578:
577:
547:
546:
534:
533:
472:
471:
370:
369:
269:
268:
164:PDCD1 - orthologs
96:
95:
92:
91:
52:Ortholog search:
6575:
6475:
6468:
6461:
6452:
6451:
4438:
4431:
4424:
4415:
4414:
4358:
4336:
4326:
4293:
4264:
4235:
4229:
4221:
4183:
4145:
4115:
4085:
4055:
4026:
3997:
3987:
3954:
3944:
3919:
3881:
3852:
3842:
3817:
3779:
3778:
3768:
3736:
3730:
3729:
3719:
3709:
3692:(49): 15016–23.
3677:
3671:
3670:
3660:
3643:(179): 179ra42.
3628:
3622:
3621:
3584:
3575:
3574:
3564:
3554:
3530:
3521:
3520:
3510:
3500:
3475:
3469:
3468:
3458:
3426:
3420:
3419:
3412:
3406:
3405:
3395:
3371:
3365:
3364:
3362:
3361:
3347:
3341:
3340:
3329:
3323:
3320:
3314:
3305:
3295:
3262:
3256:
3255:
3245:
3213:
3200:
3199:
3189:
3165:
3156:
3155:
3122:(6151): 1192–8.
3111:
3105:
3104:
3094:
3084:
3052:
3043:
3042:
3032:
3000:
2994:
2993:
2983:
2950:
2944:
2943:
2933:
2892:
2886:
2885:
2857:
2851:
2850:
2822:
2816:
2815:
2805:
2795:
2771:
2765:
2762:
2752:
2720:
2714:
2713:
2703:
2671:
2665:
2664:
2654:
2621:
2615:
2614:
2604:
2580:
2574:
2573:
2529:
2523:
2522:
2512:
2488:
2482:
2481:
2456:(5502): 319–22.
2444:
2438:
2437:
2427:
2403:
2397:
2396:
2386:
2362:
2353:
2352:
2342:
2332:
2300:
2291:
2290:
2280:
2256:
2250:
2249:
2212:
2203:
2202:
2192:
2159:
2148:
2147:
2117:
2111:
2110:
2100:
2068:
2062:
2061:
2043:
2011:
2005:
2004:
1994:
1984:
1960:
1951:
1950:
1940:
1917:The EMBO Journal
1908:
1897:
1896:
1894:
1892:
1877:
1871:
1870:
1826:
1820:
1819:
1809:
1777:
1771:
1770:
1742:
1719:
1718:
1711:
1700:
1699:
1671:
1665:
1664:
1653:
1647:
1646:
1635:
1629:
1619:
1608:
1598:
1438:) and anti-PD1 (
1176:membrane protein
1163:Kyoto University
1062:279). PD-1 is a
1029:
1028:
1000:
993:
976:
964:
963:
955:
943:
942:
939:RefSeq (protein)
929:
917:
916:
908:
896:
895:
872:
871:
853:
852:
827:
826:
804:
803:
778:
777:
759:
758:
728:
727:
588:
587:
574:
565:
558:
557:
543:
483:
481:Top expressed in
476:
475:
421:
419:Top expressed in
414:
413:
393:
392:
376:
375:
366:
353:
342:
327:
320:
314:
303:
291:
275:
274:
265:
252:
241:
226:
219:
213:
202:
188:
172:
171:
166:
117:
110:
87:
66:
65:
60:
39:
38:
33:
21:
20:
6583:
6582:
6578:
6577:
6576:
6574:
6573:
6572:
6548:
6547:
6529:
6524:
6488:
6479:
6449:
6444:
6248:
6042:
5791:
5475:
5198:
4858:
4456:
4442:
4366:
4361:
4349:(11): 2156–63.
4309:(21): 9543–53.
4223:
4222:
4032:Tissue Antigens
3888:Nature Genetics
3833:(1–2): 177–87.
3787:
3785:Further reading
3782:
3737:
3733:
3678:
3674:
3629:
3625:
3602:10.1038/nm.4022
3590:Nature Medicine
3585:
3578:
3531:
3524:
3491:(1): e1005349.
3476:
3472:
3427:
3423:
3414:
3413:
3409:
3372:
3368:
3359:
3357:
3349:
3348:
3344:
3331:
3330:
3326:
3278:(26): 2443–54.
3263:
3259:
3214:
3203:
3166:
3159:
3112:
3108:
3053:
3046:
3001:
2997:
2966:(23): 2189–99.
2951:
2947:
2908:(7528): 563–7.
2893:
2889:
2858:
2854:
2823:
2819:
2772:
2768:
2763:
2721:
2717:
2672:
2668:
2643:10.1038/nm.2106
2631:Nature Medicine
2622:
2618:
2581:
2577:
2540:(7077): 682–7.
2530:
2526:
2489:
2485:
2445:
2441:
2404:
2400:
2371:Cancer Research
2363:
2356:
2315:(19): 12293–7.
2301:
2294:
2271:(10): 5538–45.
2257:
2253:
2213:
2206:
2160:
2151:
2118:
2114:
2069:
2065:
2012:
2008:
1961:
1954:
1923:(11): 3887–95.
1909:
1900:
1890:
1888:
1878:
1874:
1827:
1823:
1778:
1774:
1743:
1722:
1713:
1712:
1703:
1672:
1668:
1655:
1654:
1650:
1637:
1636:
1632:
1620:
1611:
1599:
1590:
1586:
1577:
1560:
1555:
1481:
1475:
1463:James P Allison
1461:was awarded to
1373:
1368:
1288:
1260:dendritic cells
1240:
1204:phosphorylation
1172:
1151:
1124:PD-1 inhibitors
1038:View/Edit Mouse
1033:View/Edit Human
996:
989:
986:Location (UCSC)
972:
951:
925:
904:
817:ENSG00000276977
815:
813:ENSG00000188389
706:
645:
631:plasma membrane
614:
605:protein binding
570:
539:
530:
525:
521:
517:
513:
509:
505:
501:
497:
493:
479:
468:
463:
459:
455:
451:
447:
443:
439:
435:
431:
417:
361:
348:
340:
330:
329:
328:
321:
301:
278:Gene location (
260:
247:
239:
229:
228:
227:
220:
198:
175:Gene location (
126:
113:
106:
75:
53:
17:
12:
11:
5:
6581:
6571:
6570:
6565:
6560:
6546:
6545:
6540:
6535:
6526:
6525:
6523:
6522:
6517:
6512:
6507:
6502:
6496:
6494:
6490:
6489:
6478:
6477:
6470:
6463:
6455:
6446:
6445:
6443:
6442:
6437:
6432:
6427:
6422:
6417:
6412:
6407:
6402:
6397:
6392:
6387:
6382:
6377:
6372:
6367:
6362:
6357:
6352:
6347:
6342:
6337:
6332:
6327:
6322:
6317:
6312:
6307:
6302:
6297:
6292:
6287:
6282:
6277:
6272:
6267:
6262:
6256:
6254:
6250:
6249:
6247:
6246:
6241:
6236:
6231:
6226:
6221:
6216:
6211:
6206:
6201:
6196:
6191:
6186:
6181:
6176:
6171:
6166:
6161:
6156:
6151:
6146:
6141:
6136:
6131:
6126:
6121:
6116:
6111:
6106:
6101:
6096:
6091:
6086:
6081:
6076:
6071:
6066:
6061:
6056:
6050:
6048:
6044:
6043:
6041:
6040:
6035:
6026:
6021:
6016:
6011:
6006:
6001:
5996:
5991:
5986:
5981:
5980:
5979:
5974:
5964:
5959:
5954:
5949:
5944:
5939:
5934:
5929:
5924:
5919:
5914:
5909:
5904:
5899:
5893:
5884:
5879:
5878:
5877:
5872:
5862:
5857:
5856:
5855:
5850:
5840:
5835:
5830:
5825:
5820:
5815:
5810:
5805:
5799:
5797:
5793:
5792:
5790:
5789:
5784:
5779:
5774:
5769:
5764:
5759:
5754:
5749:
5744:
5739:
5734:
5729:
5724:
5719:
5714:
5709:
5704:
5703:
5702:
5697:
5687:
5682:
5677:
5672:
5671:
5670:
5665:
5660:
5650:
5645:
5640:
5635:
5630:
5629:
5628:
5623:
5613:
5608:
5603:
5598:
5593:
5588:
5583:
5582:
5581:
5576:
5566:
5560:
5555:
5550:
5545:
5536:
5531:
5530:
5529:
5524:
5519:
5509:
5504:
5499:
5494:
5489:
5483:
5481:
5477:
5476:
5474:
5473:
5468:
5463:
5458:
5453:
5448:
5443:
5438:
5433:
5428:
5423:
5418:
5413:
5408:
5403:
5398:
5393:
5388:
5383:
5378:
5373:
5368:
5363:
5358:
5353:
5348:
5347:
5346:
5341:
5331:
5330:
5329:
5324:
5314:
5309:
5304:
5299:
5294:
5289:
5284:
5279:
5274:
5269:
5264:
5259:
5254:
5253:
5252:
5247:
5237:
5232:
5227:
5222:
5217:
5212:
5206:
5204:
5200:
5199:
5197:
5196:
5191:
5186:
5181:
5176:
5171:
5166:
5161:
5156:
5147:
5142:
5137:
5132:
5127:
5122:
5121:
5120:
5115:
5110:
5105:
5100:
5095:
5085:
5080:
5075:
5070:
5065:
5060:
5059:
5058:
5053:
5043:
5038:
5033:
5028:
5023:
5018:
5013:
5008:
5003:
5002:
5001:
4996:
4991:
4986:
4981:
4976:
4966:
4965:
4964:
4959:
4954:
4944:
4939:
4938:
4937:
4932:
4927:
4917:
4912:
4907:
4902:
4897:
4892:
4887:
4882:
4877:
4872:
4866:
4864:
4860:
4859:
4857:
4856:
4851:
4850:
4849:
4844:
4839:
4834:
4829:
4824:
4814:
4809:
4804:
4799:
4794:
4789:
4784:
4783:
4782:
4777:
4772:
4767:
4757:
4752:
4747:
4742:
4737:
4732:
4727:
4722:
4717:
4712:
4711:
4710:
4705:
4695:
4690:
4685:
4680:
4675:
4670:
4665:
4660:
4655:
4650:
4645:
4640:
4635:
4630:
4625:
4624:
4623:
4618:
4608:
4603:
4598:
4593:
4592:
4591:
4586:
4581:
4576:
4566:
4561:
4556:
4555:
4554:
4544:
4539:
4534:
4529:
4524:
4523:
4522:
4517:
4512:
4502:
4497:
4496:
4495:
4490:
4485:
4480:
4475:
4464:
4462:
4458:
4457:
4441:
4440:
4433:
4426:
4418:
4399:
4398:
4377:
4365:
4364:External links
4362:
4360:
4359:
4337:
4294:
4265:
4236:
4184:
4152:Human Genetics
4146:
4116:
4086:
4056:
4027:
3998:
3970:(9): 1083–91.
3955:
3920:
3900:10.1038/ng1020
3882:
3853:
3818:
3788:
3786:
3783:
3781:
3780:
3751:(9): 1847–56.
3731:
3672:
3623:
3576:
3522:
3485:PLOS Pathogens
3470:
3421:
3407:
3386:(5): 573–578.
3366:
3342:
3324:
3322:
3321:
3257:
3201:
3157:
3106:
3067:(9): 4275–80.
3044:
2995:
2945:
2887:
2852:
2817:
2766:
2715:
2666:
2616:
2595:(8): 2947–53.
2575:
2524:
2483:
2439:
2398:
2354:
2292:
2251:
2204:
2175:(7): 1027–34.
2149:
2112:
2083:(10): 581–92.
2063:
2006:
1952:
1898:
1872:
1821:
1772:
1720:
1701:
1666:
1648:
1630:
1609:
1587:
1585:
1582:
1576:
1573:
1559:
1556:
1554:
1553:Animal studies
1551:
1477:Main article:
1474:
1471:
1372:
1369:
1367:
1364:
1343:and died from
1300:cardiomyopathy
1287:
1284:
1239:
1236:
1171:
1168:
1150:
1147:
1045:
1044:
1041:
1040:
1035:
1025:
1024:
1018:
1017:
1014:
1013:
1011:
1009:
1002:
1001:
994:
987:
983:
982:
979:
978:
968:
967:
961:
958:
957:
947:
946:
940:
936:
935:
932:
931:
921:
920:
914:
911:
910:
900:
899:
893:
889:
888:
885:
884:
876:
875:
869:
866:
865:
857:
856:
850:
844:
843:
840:
839:
831:
830:
824:
821:
820:
808:
807:
801:
795:
794:
791:
790:
782:
781:
775:
772:
771:
763:
762:
756:
750:
749:
744:
739:
735:
734:
724:
723:
720:
719:
708:
707:
705:
704:
699:
694:
689:
684:
679:
674:
669:
664:
659:
653:
651:
647:
646:
644:
643:
638:
633:
628:
622:
620:
616:
615:
613:
612:
607:
601:
599:
595:
594:
584:
583:
580:
579:
576:
575:
567:
566:
555:
549:
548:
545:
544:
536:
535:
532:
531:
529:
528:
524:
520:
516:
515:primary oocyte
512:
508:
504:
500:
496:
492:
488:
485:
484:
473:
470:
469:
467:
466:
462:
458:
454:
453:left ventricle
450:
446:
442:
438:
434:
430:
426:
423:
422:
410:
409:
401:
390:
384:
383:
380:RNA expression
372:
371:
368:
367:
359:
355:
354:
346:
343:
338:
332:
331:
322:
315:
309:
305:
304:
299:
293:
292:
284:
283:
271:
270:
267:
266:
258:
254:
253:
245:
242:
237:
231:
230:
221:
214:
208:
204:
203:
196:
190:
189:
181:
180:
168:
167:
124:
120:
119:
111:
103:
102:
98:
97:
94:
93:
90:
89:
71:
70:
62:
61:
50:
44:
43:
35:
34:
26:
25:
15:
9:
6:
4:
3:
2:
6580:
6569:
6568:Immune system
6566:
6564:
6561:
6559:
6556:
6555:
6553:
6544:
6541:
6539:
6536:
6534:
6531:
6530:
6521:
6518:
6516:
6513:
6511:
6508:
6506:
6503:
6501:
6498:
6497:
6495:
6491:
6487:
6483:
6476:
6471:
6469:
6464:
6462:
6457:
6456:
6453:
6441:
6438:
6436:
6433:
6431:
6428:
6426:
6423:
6421:
6418:
6416:
6413:
6411:
6408:
6406:
6403:
6401:
6398:
6396:
6393:
6391:
6388:
6386:
6383:
6381:
6378:
6376:
6373:
6371:
6368:
6366:
6363:
6361:
6358:
6356:
6353:
6351:
6348:
6346:
6343:
6341:
6338:
6336:
6333:
6331:
6328:
6326:
6323:
6321:
6318:
6316:
6313:
6311:
6308:
6306:
6303:
6301:
6298:
6296:
6293:
6291:
6288:
6286:
6283:
6281:
6278:
6276:
6273:
6271:
6268:
6266:
6263:
6261:
6258:
6257:
6255:
6251:
6245:
6242:
6240:
6237:
6235:
6232:
6230:
6227:
6225:
6222:
6220:
6217:
6215:
6212:
6210:
6207:
6205:
6202:
6200:
6197:
6195:
6192:
6190:
6187:
6185:
6182:
6180:
6177:
6175:
6172:
6170:
6167:
6165:
6162:
6160:
6157:
6155:
6152:
6150:
6147:
6145:
6142:
6140:
6137:
6135:
6132:
6130:
6127:
6125:
6122:
6120:
6117:
6115:
6112:
6110:
6107:
6105:
6102:
6100:
6097:
6095:
6092:
6090:
6087:
6085:
6082:
6080:
6077:
6075:
6072:
6070:
6067:
6065:
6062:
6060:
6057:
6055:
6052:
6051:
6049:
6045:
6039:
6036:
6034:
6030:
6027:
6025:
6022:
6020:
6017:
6015:
6012:
6010:
6007:
6005:
6002:
6000:
5997:
5995:
5992:
5990:
5987:
5985:
5982:
5978:
5975:
5973:
5970:
5969:
5968:
5965:
5963:
5960:
5958:
5955:
5953:
5950:
5948:
5945:
5943:
5940:
5938:
5935:
5933:
5930:
5928:
5925:
5923:
5920:
5918:
5915:
5913:
5910:
5908:
5905:
5903:
5900:
5897:
5894:
5892:
5888:
5885:
5883:
5880:
5876:
5873:
5871:
5868:
5867:
5866:
5863:
5861:
5858:
5854:
5851:
5849:
5846:
5845:
5844:
5841:
5839:
5836:
5834:
5831:
5829:
5826:
5824:
5821:
5819:
5816:
5814:
5811:
5809:
5806:
5804:
5801:
5800:
5798:
5794:
5788:
5785:
5783:
5780:
5778:
5775:
5773:
5770:
5768:
5765:
5763:
5760:
5758:
5755:
5753:
5750:
5748:
5745:
5743:
5740:
5738:
5735:
5733:
5730:
5728:
5725:
5723:
5720:
5718:
5715:
5713:
5710:
5708:
5705:
5701:
5698:
5696:
5693:
5692:
5691:
5688:
5686:
5683:
5681:
5678:
5676:
5673:
5669:
5666:
5664:
5661:
5659:
5656:
5655:
5654:
5651:
5649:
5646:
5644:
5641:
5639:
5636:
5634:
5631:
5627:
5624:
5622:
5619:
5618:
5617:
5614:
5612:
5609:
5607:
5604:
5602:
5599:
5597:
5594:
5592:
5589:
5587:
5584:
5580:
5577:
5575:
5572:
5571:
5570:
5567:
5564:
5561:
5559:
5556:
5554:
5551:
5549:
5546:
5544:
5540:
5537:
5535:
5532:
5528:
5525:
5523:
5520:
5518:
5515:
5514:
5513:
5510:
5508:
5505:
5503:
5500:
5498:
5495:
5493:
5490:
5488:
5485:
5484:
5482:
5478:
5472:
5469:
5467:
5464:
5462:
5459:
5457:
5454:
5452:
5449:
5447:
5444:
5442:
5439:
5437:
5434:
5432:
5429:
5427:
5424:
5422:
5419:
5417:
5414:
5412:
5409:
5407:
5404:
5402:
5399:
5397:
5394:
5392:
5389:
5387:
5384:
5382:
5379:
5377:
5374:
5372:
5369:
5367:
5364:
5362:
5359:
5357:
5354:
5352:
5349:
5345:
5342:
5340:
5337:
5336:
5335:
5332:
5328:
5325:
5323:
5320:
5319:
5318:
5315:
5313:
5310:
5308:
5305:
5303:
5300:
5298:
5295:
5293:
5290:
5288:
5285:
5283:
5280:
5278:
5275:
5273:
5270:
5268:
5265:
5263:
5260:
5258:
5255:
5251:
5248:
5246:
5243:
5242:
5241:
5238:
5236:
5233:
5231:
5228:
5226:
5223:
5221:
5218:
5216:
5213:
5211:
5208:
5207:
5205:
5201:
5195:
5192:
5190:
5187:
5185:
5182:
5180:
5177:
5175:
5172:
5170:
5167:
5165:
5162:
5160:
5157:
5155:
5151:
5148:
5146:
5143:
5141:
5138:
5136:
5133:
5131:
5128:
5126:
5123:
5119:
5116:
5114:
5111:
5109:
5106:
5104:
5101:
5099:
5096:
5094:
5091:
5090:
5089:
5086:
5084:
5081:
5079:
5076:
5074:
5071:
5069:
5066:
5064:
5061:
5057:
5054:
5052:
5049:
5048:
5047:
5044:
5042:
5039:
5037:
5034:
5032:
5029:
5027:
5024:
5022:
5019:
5017:
5014:
5012:
5009:
5007:
5004:
5000:
4997:
4995:
4992:
4990:
4987:
4985:
4982:
4980:
4977:
4975:
4972:
4971:
4970:
4967:
4963:
4960:
4958:
4955:
4953:
4950:
4949:
4948:
4945:
4943:
4940:
4936:
4933:
4931:
4928:
4926:
4923:
4922:
4921:
4918:
4916:
4913:
4911:
4908:
4906:
4903:
4901:
4898:
4896:
4893:
4891:
4888:
4886:
4883:
4881:
4878:
4876:
4873:
4871:
4868:
4867:
4865:
4861:
4855:
4852:
4848:
4845:
4843:
4840:
4838:
4835:
4833:
4830:
4828:
4825:
4823:
4820:
4819:
4818:
4815:
4813:
4810:
4808:
4805:
4803:
4800:
4798:
4795:
4793:
4790:
4788:
4785:
4781:
4778:
4776:
4773:
4771:
4768:
4766:
4763:
4762:
4761:
4758:
4756:
4753:
4751:
4748:
4746:
4743:
4741:
4738:
4736:
4733:
4731:
4728:
4726:
4723:
4721:
4718:
4716:
4713:
4709:
4706:
4704:
4701:
4700:
4699:
4696:
4694:
4691:
4689:
4686:
4684:
4681:
4679:
4676:
4674:
4671:
4669:
4666:
4664:
4661:
4659:
4656:
4654:
4651:
4649:
4646:
4644:
4641:
4639:
4636:
4634:
4631:
4629:
4626:
4622:
4619:
4617:
4614:
4613:
4612:
4609:
4607:
4604:
4602:
4599:
4597:
4594:
4590:
4587:
4585:
4582:
4580:
4577:
4575:
4572:
4571:
4570:
4567:
4565:
4562:
4560:
4557:
4553:
4550:
4549:
4548:
4545:
4543:
4540:
4538:
4535:
4533:
4530:
4528:
4525:
4521:
4518:
4516:
4513:
4511:
4508:
4507:
4506:
4503:
4501:
4498:
4494:
4491:
4489:
4486:
4484:
4481:
4479:
4476:
4474:
4471:
4470:
4469:
4466:
4465:
4463:
4459:
4454:
4450:
4446:
4439:
4434:
4432:
4427:
4425:
4420:
4419:
4416:
4412:
4411:
4409:
4408:public domain
4405:
4396:
4392:
4391:
4386:
4382:
4378:
4375:
4371:
4368:
4367:
4356:
4352:
4348:
4344:
4338:
4334:
4330:
4325:
4320:
4316:
4312:
4308:
4304:
4300:
4295:
4291:
4287:
4283:
4279:
4276:(2): 109–16.
4275:
4271:
4266:
4262:
4258:
4254:
4250:
4247:(6): 1665–9.
4246:
4242:
4237:
4233:
4227:
4219:
4215:
4211:
4207:
4203:
4199:
4195:
4191:
4185:
4181:
4177:
4173:
4169:
4165:
4161:
4157:
4153:
4147:
4143:
4139:
4135:
4131:
4128:(6): 1770–3.
4127:
4123:
4117:
4113:
4109:
4105:
4101:
4097:
4093:
4087:
4083:
4079:
4075:
4071:
4067:
4063:
4057:
4053:
4049:
4045:
4041:
4037:
4033:
4028:
4024:
4020:
4016:
4012:
4008:
4004:
3999:
3995:
3991:
3986:
3981:
3977:
3973:
3969:
3965:
3961:
3956:
3952:
3948:
3943:
3938:
3934:
3930:
3926:
3921:
3917:
3913:
3909:
3905:
3901:
3897:
3893:
3889:
3883:
3879:
3875:
3871:
3867:
3864:(3): 215–20.
3863:
3859:
3854:
3850:
3846:
3841:
3836:
3832:
3828:
3824:
3819:
3815:
3811:
3807:
3803:
3799:
3795:
3790:
3789:
3776:
3772:
3767:
3762:
3758:
3754:
3750:
3746:
3742:
3735:
3727:
3723:
3718:
3713:
3708:
3703:
3699:
3695:
3691:
3687:
3683:
3676:
3668:
3664:
3659:
3654:
3650:
3646:
3642:
3638:
3634:
3627:
3619:
3615:
3611:
3607:
3603:
3599:
3595:
3591:
3583:
3581:
3572:
3568:
3563:
3558:
3553:
3548:
3544:
3540:
3539:Retrovirology
3536:
3529:
3527:
3518:
3514:
3509:
3504:
3499:
3494:
3490:
3486:
3482:
3474:
3466:
3462:
3457:
3452:
3448:
3444:
3440:
3436:
3432:
3425:
3417:
3411:
3403:
3399:
3394:
3389:
3385:
3381:
3377:
3370:
3356:
3352:
3346:
3338:
3334:
3328:
3318:
3313:
3307:
3306:
3303:
3299:
3294:
3289:
3285:
3281:
3277:
3273:
3269:
3261:
3253:
3249:
3244:
3239:
3235:
3231:
3228:(5): 275–87.
3227:
3223:
3219:
3212:
3210:
3208:
3206:
3197:
3193:
3188:
3183:
3179:
3175:
3171:
3164:
3162:
3153:
3149:
3145:
3141:
3137:
3133:
3129:
3125:
3121:
3117:
3110:
3102:
3098:
3093:
3088:
3083:
3078:
3074:
3070:
3066:
3062:
3058:
3051:
3049:
3040:
3036:
3031:
3026:
3022:
3018:
3015:(1): 98–106.
3014:
3010:
3006:
2999:
2991:
2987:
2982:
2977:
2973:
2969:
2965:
2961:
2957:
2949:
2941:
2937:
2932:
2927:
2923:
2919:
2915:
2911:
2907:
2903:
2899:
2891:
2883:
2879:
2875:
2871:
2867:
2863:
2856:
2848:
2844:
2840:
2836:
2832:
2828:
2821:
2813:
2809:
2804:
2799:
2794:
2789:
2785:
2781:
2777:
2770:
2760:
2756:
2751:
2746:
2742:
2738:
2734:
2730:
2726:
2719:
2711:
2707:
2702:
2697:
2693:
2689:
2686:(4): 265–76.
2685:
2681:
2677:
2670:
2662:
2658:
2653:
2648:
2644:
2640:
2636:
2632:
2628:
2620:
2612:
2608:
2603:
2598:
2594:
2590:
2586:
2579:
2571:
2567:
2563:
2559:
2555:
2551:
2547:
2543:
2539:
2535:
2528:
2520:
2516:
2511:
2506:
2503:(3): 634–43.
2502:
2498:
2494:
2487:
2479:
2475:
2471:
2467:
2463:
2459:
2455:
2451:
2443:
2435:
2431:
2426:
2421:
2418:(2): 141–51.
2417:
2413:
2409:
2402:
2394:
2390:
2385:
2380:
2377:(3): 1140–5.
2376:
2372:
2368:
2361:
2359:
2350:
2346:
2341:
2336:
2331:
2326:
2322:
2318:
2314:
2310:
2306:
2299:
2297:
2288:
2284:
2279:
2274:
2270:
2266:
2262:
2255:
2247:
2243:
2239:
2235:
2231:
2230:10.1038/85330
2227:
2223:
2219:
2211:
2209:
2200:
2196:
2191:
2186:
2182:
2178:
2174:
2170:
2166:
2158:
2156:
2154:
2145:
2141:
2137:
2133:
2130:(5): 765–72.
2129:
2125:
2124:
2116:
2108:
2104:
2099:
2094:
2090:
2086:
2082:
2078:
2074:
2067:
2059:
2055:
2051:
2047:
2042:
2037:
2033:
2029:
2026:(5): 739–45.
2025:
2021:
2017:
2010:
2002:
1998:
1993:
1988:
1983:
1978:
1974:
1970:
1966:
1959:
1957:
1948:
1944:
1939:
1934:
1930:
1926:
1922:
1918:
1914:
1907:
1905:
1903:
1887:
1883:
1876:
1868:
1864:
1860:
1856:
1852:
1848:
1844:
1840:
1836:
1832:
1825:
1817:
1813:
1808:
1803:
1799:
1795:
1791:
1787:
1783:
1776:
1768:
1764:
1760:
1756:
1752:
1748:
1741:
1739:
1737:
1735:
1733:
1731:
1729:
1727:
1725:
1716:
1710:
1708:
1706:
1697:
1693:
1689:
1685:
1681:
1677:
1670:
1662:
1658:
1652:
1644:
1640:
1634:
1627:
1623:
1618:
1616:
1614:
1606:
1602:
1597:
1595:
1593:
1588:
1581:
1572:
1569:
1565:
1550:
1548:
1544:
1540:
1536:
1532:
1528:
1524:
1519:
1517:
1513:
1511:
1507:
1506:Pembrolizumab
1503:
1501:
1497:
1493:
1489:
1484:
1480:
1470:
1468:
1464:
1460:
1455:
1451:
1448:
1443:
1441:
1437:
1431:
1429:
1423:
1421:
1417:
1412:
1410:
1406:
1402:
1398:
1397:immune system
1394:
1386:
1382:
1377:
1363:
1361:
1356:
1354:
1350:
1346:
1342:
1338:
1334:
1329:
1325:
1322:
1317:
1313:
1308:
1305:
1301:
1297:
1293:
1292:knockout mice
1283:
1281:
1277:
1273:
1269:
1265:
1261:
1257:
1253:
1249:
1245:
1242:PD-1 has two
1235:
1233:
1229:
1225:
1221:
1217:
1213:
1209:
1205:
1201:
1200:transmembrane
1197:
1193:
1189:
1185:
1181:
1177:
1167:
1164:
1160:
1156:
1146:
1144:
1140:
1136:
1132:
1127:
1125:
1121:
1119:
1115:
1111:
1107:
1103:
1098:
1096:
1092:
1088:
1087:immune system
1084:
1080:
1076:
1072:
1069:
1065:
1061:
1058:
1054:
1051:
1039:
1034:
1030:
1026:
1023:
1019:
1012:
1010:
1007:
1003:
999:
995:
992:
988:
984:
977:
975:
969:
965:
962:
956:
954:
948:
944:
941:
937:
930:
928:
922:
918:
915:
909:
907:
901:
897:
894:
892:RefSeq (mRNA)
890:
883:
882:
877:
873:
870:
864:
863:
858:
854:
851:
849:
845:
838:
837:
832:
828:
825:
819:
818:
814:
809:
805:
802:
800:
796:
789:
788:
783:
779:
776:
770:
769:
764:
760:
757:
755:
751:
748:
745:
743:
740:
736:
733:
729:
725:
718:
714:
709:
703:
700:
698:
695:
693:
690:
688:
685:
683:
680:
678:
675:
673:
670:
668:
665:
663:
660:
658:
655:
654:
652:
649:
648:
642:
639:
637:
634:
632:
629:
627:
624:
623:
621:
618:
617:
611:
608:
606:
603:
602:
600:
597:
596:
593:
592:Gene ontology
589:
585:
573:
568:
564:
559:
556:
554:
550:
542:
537:
526:
522:
518:
514:
510:
506:
502:
498:
494:
490:
489:
486:
482:
477:
474:
464:
460:
456:
452:
448:
444:
441:right auricle
440:
436:
432:
428:
427:
424:
420:
415:
412:
411:
408:
406:
402:
400:
399:
395:
394:
391:
389:
385:
381:
377:
373:
365:
360:
356:
352:
347:
337:
333:
326:
319:
313:
306:
298:
294:
290:
285:
281:
276:
272:
264:
259:
255:
251:
246:
236:
232:
225:
218:
212:
205:
201:
195:
191:
187:
182:
178:
173:
169:
165:
161:
157:
153:
149:
145:
141:
137:
133:
129:
121:
116:
109:
104:
99:
88:
86:
82:
78:
72:
67:
64:
63:
59:
56:
49:
45:
40:
36:
32:
27:
22:
19:
6163:
5966:
5886:
5864:
5842:
5689:
5652:
5615:
5568:
5538:
5511:
5333:
5239:
5087:
4816:
4568:
4401:
4400:
4388:
4346:
4342:
4306:
4302:
4273:
4269:
4244:
4240:
4226:cite journal
4196:(7): 510–6.
4193:
4189:
4158:(5): 393–8.
4155:
4151:
4125:
4121:
4098:(3): 770–5.
4095:
4091:
4068:(1): 327–8.
4065:
4061:
4038:(6): 492–7.
4035:
4031:
4009:(3): 672–7.
4006:
4002:
3967:
3963:
3935:(2): 711–8.
3932:
3928:
3894:(4): 666–9.
3891:
3887:
3861:
3857:
3830:
3826:
3797:
3793:
3748:
3744:
3734:
3689:
3685:
3675:
3640:
3636:
3626:
3596:(2): 135–7.
3593:
3589:
3542:
3538:
3488:
3484:
3473:
3441:(1): 81–90.
3438:
3434:
3424:
3410:
3383:
3379:
3369:
3358:. Retrieved
3354:
3345:
3336:
3327:
3316:
3275:
3271:
3260:
3225:
3221:
3177:
3173:
3119:
3115:
3109:
3064:
3060:
3012:
3008:
2998:
2963:
2959:
2948:
2905:
2901:
2890:
2868:(5): 430–9.
2865:
2861:
2855:
2830:
2826:
2820:
2783:
2779:
2769:
2732:
2728:
2718:
2683:
2679:
2669:
2637:(4): 452–9.
2634:
2630:
2619:
2592:
2588:
2578:
2537:
2533:
2527:
2500:
2496:
2486:
2453:
2449:
2442:
2415:
2411:
2401:
2374:
2370:
2312:
2308:
2268:
2264:
2254:
2224:(3): 261–8.
2221:
2217:
2172:
2168:
2127:
2121:
2115:
2080:
2076:
2066:
2023:
2019:
2009:
1972:
1968:
1920:
1916:
1889:. Retrieved
1885:
1875:
1837:(1): 45–59.
1834:
1830:
1824:
1789:
1785:
1775:
1750:
1746:
1682:(3): 704–6.
1679:
1675:
1669:
1660:
1651:
1642:
1633:
1578:
1561:
1535:atezolizumab
1520:
1514:
1504:
1490:, (Opdivo -
1485:
1482:
1467:Tasuku Honjo
1456:
1452:
1444:
1432:
1428:CD8+ T cells
1424:
1413:
1404:
1390:
1357:
1330:
1326:
1309:
1298:and dilated
1289:
1276:B16 melanoma
1241:
1173:
1159:Tasuku Honjo
1152:
1128:
1122:
1099:
1073:. PD-1 is a
1067:
1056:
1052:
1049:
1048:
971:
950:
924:
903:
879:
860:
834:
811:
785:
766:
746:
741:
511:cumulus cell
403:
396:
261:241,858,894
248:241,849,884
123:External IDs
74:
18:
3800:(1): 25–8.
3180:(1): 1–10.
2786:: 5023–39.
1527:pidilizumab
1516:Toripalimab
1232:macrophages
1180:amino acids
1114:lymph nodes
1100:PD-1 is an
433:granulocyte
362:93,980,278
349:93,966,027
101:Identifiers
6552:Categories
4451:(see also
3360:2019-08-25
2729:Oncotarget
1792:: 219–42.
1628:, May 2017
1607:, May 2017
1584:References
1531:BMS-936559
1525:) include
1436:ipilimumab
1333:thymocytes
1190:family of
429:lymph node
407:(ortholog)
341:1|1 D
144:HomoloGene
6493:receptors
2833:: 88–98.
2570:205210800
1496:Nivolumab
1488:nivolumab
1457:The 2018
1440:nivolumab
1337:apoptosis
1170:Structure
1155:apoptosis
1149:Discovery
1106:apoptosis
974:NP_032824
953:NP_005009
927:NM_008798
906:NM_005018
732:Orthologs
152:GeneCards
4445:Proteins
4355:16265694
4333:16227604
4290:16171790
4261:15934088
4218:33705026
4210:15352422
4172:15322919
4142:15188352
4112:15022318
4082:14730631
4052:14617032
4023:12893276
3994:12719480
3951:12517932
3916:20496046
3908:12402038
3878:12095712
3775:25073790
3726:26621719
3667:23552370
3618:20699898
3610:26779813
3571:25756928
3517:26741490
3465:22198819
3402:30805896
3302:22658127
3252:27079802
3196:23890059
3174:Immunity
3152:29830409
3144:24031011
3101:20160101
3039:26558876
2990:25409260
2940:25428504
2882:21074057
2847:26895815
2812:27574444
2759:28881780
2710:25797516
2661:20208540
2611:15837746
2562:16382236
2519:11857337
2478:11209085
2434:10485649
2412:Immunity
2393:14871849
2349:12218188
2287:12421930
2246:27659586
2238:11224527
2199:11015443
2107:21739608
2058:11384162
2050:17195077
2041:11030209
2001:28018338
1867:23843848
1859:21276005
1816:20636820
1767:29208439
1676:Genomics
1624:–
1603:–
1539:avelumab
1510:melanoma
1500:melanoma
1405:in vitro
1335:undergo
1286:Function
1022:Wikidata
711:Sources:
636:membrane
445:appendix
6253:301–350
6047:251–300
5999:CD240CE
5796:201–250
5480:151–200
5203:101–150
4395:PDBe-KB
4385:UniProt
4324:1265804
4180:8562917
3985:2193977
3849:9332365
3814:9141617
3766:4144739
3717:4679000
3694:Bibcode
3658:3684024
3562:4340294
3508:4704737
3456:3731769
3293:3544539
3243:5381938
3124:Bibcode
3116:Science
3092:2840093
3069:Bibcode
3030:4892769
2981:4315319
2931:4836193
2910:Bibcode
2803:4990391
2750:5581079
2701:4393798
2652:4229134
2542:Bibcode
2458:Bibcode
2450:Science
2317:Bibcode
2190:2193311
2144:8671665
2098:3191120
1992:5149523
1975:: 550.
1947:1396582
1839:Bibcode
1807:2919275
1696:7851902
1626:Ensembl
1605:Ensembl
1244:ligands
1238:Ligands
1228:B cells
1178:of 288
1135:ligands
1110:antigen
1083:B cells
1079:T cells
1064:protein
848:UniProt
799:Ensembl
738:Species
717:QuickGO
382:pattern
108:Aliases
6510:CTLA-4
6260:CD300A
6219:CDw293
6004:CD240D
5865:CD213a
5843:CDw210
5808:CD202b
5782:CDw199
5777:CDw198
5431:CD140b
4863:51–100
4390:Q15116
4376:(MeSH)
4353:
4331:
4321:
4288:
4259:
4216:
4208:
4178:
4170:
4140:
4110:
4080:
4050:
4021:
3992:
3982:
3949:
3914:
3906:
3876:
3847:
3812:
3773:
3763:
3724:
3714:
3665:
3655:
3616:
3608:
3569:
3559:
3545:: 14.
3515:
3505:
3463:
3453:
3400:
3300:
3290:
3250:
3240:
3194:
3150:
3142:
3099:
3089:
3037:
3027:
2988:
2978:
2938:
2928:
2902:Nature
2880:
2845:
2810:
2800:
2757:
2747:
2708:
2698:
2659:
2649:
2609:
2568:
2560:
2534:Nature
2517:
2476:
2432:
2391:
2347:
2340:129438
2337:
2285:
2244:
2236:
2197:
2187:
2142:
2105:
2095:
2056:
2048:
2038:
1999:
1989:
1945:
1938:556898
1935:
1891:24 Nov
1865:
1857:
1814:
1804:
1765:
1694:
1547:Pfizer
1401:cancer
1371:Cancer
1349:T cell
1268:GM-CSF
1230:, and
1192:T cell
1188:CTLA-4
1091:T cell
1053:(PD-1)
1008:search
1006:PubMed
881:Q02242
862:Q15116
754:Entrez
553:BioGPS
519:spleen
507:zygote
499:embryo
495:thymus
491:embryo
465:tonsil
437:spleen
240:2q37.3
140:104879
132:600244
6440:CD350
6435:CD349
6430:CD344
6425:CD340
6420:CD339
6415:CD338
6410:CD337
6405:CD336
6400:CD335
6395:CD334
6390:CD333
6385:CD332
6380:CD331
6375:CD329
6370:CD328
6365:CD327
6360:CD326
6355:CD325
6350:CD324
6345:CD322
6340:CD321
6335:CD320
6330:CD318
6325:CD317
6320:CD316
6315:CD315
6310:CD314
6305:CD312
6300:CD309
6295:CD307
6290:CD306
6285:CD305
6280:CD304
6275:CD303
6270:CD302
6265:CD301
6244:CD299
6239:CD298
6234:CD297
6229:CD295
6224:CD294
6214:CD292
6209:CD290
6204:CD289
6199:CD288
6194:CD286
6189:CD284
6184:CD283
6179:CD282
6174:CD281
6169:CD280
6164:CD279
6159:CD278
6154:CD276
6149:CD275
6144:CD274
6139:CD273
6134:CD272
6129:CD271
6124:CD269
6119:CD268
6114:CD267
6109:CD266
6104:CD265
6099:CD264
6094:CD263
6089:CD262
6084:CD261
6079:CD258
6074:CD257
6069:CD256
6064:CD254
6059:CD253
6054:CD252
6038:CD249
6033:CD248
6029:CD247
6024:CD246
6019:CD244
6014:CD243
6009:CD241
5994:CD239
5989:CD238
5984:CD236
5967:CD235
5962:CD234
5957:CD233
5952:CD230
5947:CD229
5942:CD228
5937:CD227
5932:CD226
5927:CD225
5922:CD224
5917:CD223
5912:CD222
5907:CD221
5902:CD220
5887:CD218
5882:CD217
5860:CD212
5838:CD209
5833:CD208
5828:CD207
5823:CD206
5818:CD205
5813:CD204
5803:CD201
5787:CD200
5772:CD197
5767:CD196
5762:CD195
5757:CD194
5752:CD193
5747:CD192
5742:CD191
5737:CD186
5732:CD185
5727:CD184
5722:CD183
5717:CD182
5712:CD181
5707:CD180
5690:CD179
5685:CD178
5680:CD177
5675:CD174
5653:CD172
5648:CD171
5643:CD170
5638:CD169
5633:CD168
5616:CD167
5611:CD166
5606:CD164
5601:CD163
5596:CD162
5591:CD161
5586:CD160
5569:CD159
5539:CD158
5534:CD157
5512:CD156
5507:CD155
5502:CD154
5497:CD153
5492:CD152
5487:CD151
5471:CD150
5466:CD148
5461:CD147
5456:CD146
5451:CD144
5446:CD143
5441:CD142
5436:CD141
5426:CD138
5421:CD137
5416:CD136
5411:CD135
5406:CD134
5401:CD133
5396:CD132
5391:CD131
5386:CD130
5381:CD129
5376:CD127
5371:CD126
5366:CD125
5361:CD124
5356:CD123
5351:CD122
5334:CD121
5317:CD120
5312:CD119
5307:CD118
5302:CD117
5297:CD116
5292:CD115
5287:CD114
5282:CD113
5277:CD112
5272:CD111
5267:CD110
5262:CD109
5257:CD108
5240:CD107
5235:CD106
5230:CD105
5225:CD104
5220:CD103
5215:CD102
5210:CD101
5194:CD100
4214:S2CID
4190:Lupus
4176:S2CID
3912:S2CID
3614:S2CID
3380:Drugs
3148:S2CID
2566:S2CID
2242:S2CID
2054:S2CID
1863:S2CID
1564:TIGIT
1447:PD-L1
1416:CTLA4
1280:IFN-γ
1252:PD-L2
1248:PD-L1
1224:CBL-b
1220:SHP-2
1216:SHP-1
1143:PD-L2
1139:PD-L1
1068:PDCD1
1057:CD279
787:18566
747:Mouse
742:Human
713:Amigo
527:ovary
523:blood
449:blood
405:Mouse
398:Human
345:Start
280:Mouse
244:Start
177:Human
156:PDCD1
115:PDCD1
24:PDCD1
6520:PD-1
6515:ICOS
6505:CD28
6500:BTLA
5189:CD99
5184:CD98
5179:CD97
5174:CD96
5169:CD95
5164:CD94
5159:CD93
5154:CD92
5150:CD91
5145:CD90
5140:CD89
5135:CD88
5130:CD87
5125:CD86
5088:CD85
5083:CD84
5078:CD83
5073:CD82
5068:CD81
5063:CD80
5046:CD79
5041:CD78
5036:CD74
5031:CD73
5026:CD72
5021:CD71
5016:CD70
5011:CD69
5006:CD68
4969:CD66
4947:CD64
4942:CD63
4920:CD62
4915:CD61
4910:CD59
4905:CD58
4900:CD57
4895:CD56
4890:CD55
4885:CD54
4880:CD53
4875:CD52
4870:CD51
4854:CD50
4817:CD49
4812:CD48
4807:CD47
4802:CD46
4797:CD45
4792:CD44
4787:CD43
4760:CD42
4755:CD41
4750:CD40
4745:CD39
4740:CD38
4735:CD37
4730:CD36
4725:CD35
4720:CD34
4715:CD33
4698:CD32
4693:CD31
4688:CD30
4683:CD29
4678:CD28
4673:CD27
4668:CD26
4663:CD25
4658:CD24
4653:CD23
4648:CD22
4643:CD21
4638:CD20
4633:CD19
4628:CD18
4611:CD16
4606:CD15
4601:CD14
4596:CD13
4569:CD11
4564:CD10
4461:1–50
4383:for
4351:PMID
4329:PMID
4286:PMID
4257:PMID
4232:link
4206:PMID
4168:PMID
4138:PMID
4108:PMID
4078:PMID
4048:PMID
4019:PMID
3990:PMID
3947:PMID
3904:PMID
3874:PMID
3845:PMID
3827:Gene
3810:PMID
3771:PMID
3722:PMID
3663:PMID
3606:PMID
3567:PMID
3513:PMID
3461:PMID
3398:PMID
3298:PMID
3248:PMID
3192:PMID
3140:PMID
3097:PMID
3035:PMID
2986:PMID
2936:PMID
2878:PMID
2843:PMID
2808:PMID
2755:PMID
2706:PMID
2657:PMID
2607:PMID
2558:PMID
2515:PMID
2474:PMID
2430:PMID
2389:PMID
2345:PMID
2283:PMID
2234:PMID
2195:PMID
2140:PMID
2103:PMID
2046:PMID
1997:PMID
1943:PMID
1893:2014
1855:PMID
1835:1217
1812:PMID
1763:PMID
1692:PMID
1545:and
1465:and
1321:LCMV
1314:and
1272:mRNA
1266:and
1250:and
1218:and
1184:CD28
1141:and
1081:and
1071:gene
768:5133
388:Bgee
336:Band
297:Chr.
235:Band
194:Chr.
148:3681
128:OMIM
85:4ZQK
81:3RRQ
77:2M2D
58:RCSB
55:PDBe
4559:CD9
4547:CD8
4542:CD7
4537:CD6
4532:CD5
4527:CD4
4505:CD3
4500:CD2
4473:a-c
4468:CD1
4381:PDB
4319:PMC
4311:doi
4278:doi
4274:235
4249:doi
4198:doi
4160:doi
4156:115
4130:doi
4100:doi
4070:doi
4040:doi
4011:doi
4007:307
3980:PMC
3972:doi
3968:197
3937:doi
3933:170
3896:doi
3866:doi
3835:doi
3831:197
3802:doi
3798:232
3761:PMC
3753:doi
3749:211
3712:PMC
3702:doi
3690:112
3653:PMC
3645:doi
3598:doi
3557:PMC
3547:doi
3503:PMC
3493:doi
3451:PMC
3443:doi
3388:doi
3288:PMC
3280:doi
3276:366
3238:PMC
3230:doi
3182:doi
3132:doi
3120:341
3087:PMC
3077:doi
3065:107
3025:PMC
3017:doi
2976:PMC
2968:doi
2964:371
2926:PMC
2918:doi
2906:515
2870:doi
2835:doi
2831:100
2798:PMC
2788:doi
2745:PMC
2737:doi
2696:PMC
2688:doi
2647:PMC
2639:doi
2597:doi
2550:doi
2538:439
2505:doi
2466:doi
2454:291
2420:doi
2379:doi
2335:PMC
2325:doi
2273:doi
2269:169
2226:doi
2185:PMC
2177:doi
2173:192
2132:doi
2093:PMC
2085:doi
2036:PMC
2028:doi
1987:PMC
1977:doi
1933:PMC
1925:doi
1847:doi
1802:PMC
1794:doi
1790:236
1755:doi
1684:doi
1568:HIV
1558:HIV
1316:CD8
1312:CD4
1304:CD3
1264:LPS
1212:TCR
1196:IgV
1077:on
1055:, (
358:End
257:End
160:OMA
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